The effect of optogenetic Gq-induced astrocytic Ca2+ signaling on memory and blood flow

Hajime Hirase

Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark

Several lines of in vitro evidence support that activation of astrocytic G protein-coupled receptors (GPCRs) leads to the secretion of molecules that modulate synaptic plasticity. To address this in the live mouse brain, transgenic mice with astrocytic expression of the optogenetic Gq-type GPCR (Optoα1AR) were established. We demonstrate that brief blue light illumination on the cortex induces transient Ca2+ elevations in astrocytes, which are similar to those observed in wild-type mice. Moreover, the activation of cortical astrocytes resulted in an adenosine A1 receptor-dependent inhibition of neuronal activity. At the behavioral level, repeated astrocytic activation in the anterior cortex gradually affected novel open field exploratory behavior. Moreover, anterior cortex astrocyte activation led to enhanced remote memory in a novel object recognition task, while it had little impact on Y-maze (working memory). Anatomically, astrocytes enwrap the vasculature by their endfoot processes. To understand the role of astrocytic Ca2+ signaling in local blood flow regulation, we have devised viral vectors that label the blood plasma with fluorescence for months. Nonetheless, astrocytic Gq-mediated effects on local cerebral blood flow appear rather inert using this least invasive and astrocyte-specific activation/optical imaging method.

Invité par Xavier Leinekugel

Lundi 18 septembre 2023 à 11h – salle de conférence de l’Inmed